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Updated: Jan 9, 2026
Author Spotlight: Exploring the Role of Inflammation in the Co-occurrence of Primary Sjogren's Syndrome and Lung Adenocarcinoma
Published on: September 20, 2024
The Role of Inflammatory Cytokines in the Causal Pathway From Gut Microbiota to Sjögren's Syndrome: Evidence From
Junkang Zhao1,2,3, Jiannan Han1,4, Xiuying Fan1
1Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan 030032, Shanxi, China.
Purpose:
Evidence is accumulating that links gut microbiota, a crucial component of the immune environment, to Sjogren's syndrome (SS). The mechanisms underlying the influence of gut microbiota on the onset and development of SS are still not completely understood. To this end, we applied a Mendelian randomization (MR) framework to investigate whether inflammatory cytokines mediate the association of gut microbiota with SS.
Methods:
Our MR analysis leveraged publicly available GWAS data, including information on 211 gut microbiota taxa sourced from the MiBioGen consortium (18,340 participants), summary statistics for 91 inflammatory cytokines obtained from a study of 14,824 individuals, and genetic data for SS derived from the UK Biobank (407,746 participants). To investigate causal associations between gut microbiota and SS, we primarily employed the inverse variance weighted method, supported by additional techniques such as MR-Egger, simple mode, weighted median, and weighted mode for validation. The potential mediating effect of inflammatory cytokines in the gut microbiota-SS relationship was investigated using both mediation MR and multivariable MR (MVMR) analyses.
Results:
MR analysis identified five microbiota taxa causally associated with SS. Particularly, class Gammaproteobacteria (OR = 3.468, 95% CI = 1.139-10.557, p=0.029) and genus Peptococcus (OR = 1.722, 95% CI = 1.082-2.471, p=0.022) were significantly associated with an increased risk of developing SS. Six inflammatory cytokines were identified as potentially causal, with Axin-1 (OR = 2.556, 95% CI = 1.072-6.096, p=0.034) and C-X-C motif chemokine 10 levels (CXCL10) (OR = 3.049, 95% CI = 1.428-6.513, p=0.004) being the most critical contributors. Mediation MR analysis showed that Axin-1 levels mediated 16.96% of the causal effect of class Gammaproteobacteria on SS, CXCL10 levels mediated 36.78% of the causal effect of genus Coprococcus3 on SS.
Conclusion:
The findings suggest that certain gut microbiota is sociated with an increased risk of SS, mediated by specific inflammatory cytokines.
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